Social relationships are fundamental determinants of psychological health and well-being. Poor quality relationships and social isolation heighten vulnerability to and exacerbate a myriad of negative mental health outcomes (e.g., anxiety, depression, suicide), which create substantial costs to the individual and society. Although the biobehavioral processes that support the formation of positive social relationships are well- delineated, a fundamental gap exists in translating that knowledge to develop mechanism-informed interventions for psychiatric conditions. The proposed project seeks to fill this gap by testing a neurally- mediated pathway for enhancing social connections through an experimental medicine approach. We draw on research implicating the positive valence system (PVS), a core dimension of the Research Domain Criteria (RDoC) framework, as a fundamental mechanism that promotes social affiliation and attachment. Building on our initial treatment development work, we will evaluate the effects of a novel psychosocial intervention ? social approach training ? designed to up-regulate components of the PVS (social approach motivation and reward responsiveness, or ?social reward sensitivity?) in treatment-seeking individuals with anxiety or depression who present with social functioning impairments. R61 phase: Aim 1 will test the hypothesis that social approach training can up-regulate social reward sensitivity (intervention target) across neural, physiological, behavioral, and self-report units of analysis in n=60 patients randomized to one of two treatment doses, or a no intervention control condition. Aim 2 will investigate optimal dosing of social approach training to maximally engage the target. Aim 3 will establish further psychometric support (e.g., test-retest reliability) for the proposed measures of target engagement. R33 Phase: Pending initial demonstration that social approach training modulates social reward sensitivity (R61-Aim 1), Aim 1 of the R33 phase seeks to replicate evidence of target engagement by comparing participants randomized to receive the optimal dose of social approach training (n=50) or to an active control condition (stress management training; n=50). Aim 2 will examine whether changes in social reward sensitivity are associated with improvements in the frequency and strength of social connections assessed through self-report, social network surveys, and observation of real-world social behavior acquired through social media. Through this approach we will gain unprecedented ecological validity to ascertain the impact of the intervention on real-world functioning, a high priority of the NIMH Strategic Plan. We will also explore changes in mental health outcomes following treatment. By targeting social approach mechanisms rather than disorder-bound symptoms, and linking changes in neural circuit function to changes in real-world social connections, we will (1) deepen our understanding of the mechanisms that support positive connections with others, and (2) advance neuroscience-informed and targeted intervention approaches with the potential to yield clinically meaningful outcomes with measurable real-world impact.